Neisseria gonorrhoeae

1
Neisseria gonorrhoeae

• Nealia House

2
Gonorrhea

• Topic Overview
• Biology of Neisseria gonorrhoeae
• Survival Within Host
• Screening
• Treatment
• Control/Surveillance

http//www2.chemie.uni-erlangen.de/education/medch
em/harnsteine/urs_infektion.html
3
Gonorrhea

• Sexually transmitted disease
• Infection Rate
• socioeconomic class
• Age
• Very common infectious disease
• STI second only to chlamydia
• Increasing antibacterial resistance
• Increases efficiency of HIV transmission

http//www.cat.cc.md.us/courses/bio141/labmanua/la
b1/dkngon.html
4
Affected Populations
STI Rates World-Wide
http//www.agi-usa.org/pubs/ib_std.html
5
Gonorrhea

• Humans only natural host
• Reproductive tract
• Infection can be asymptomatic
• Infertility
• Several tests available for detection of gonorrhea

http//evolution.berkeley.edu/evosite/relevance/im
ages/Kunkel_97210C.jpg
6
Gonorrhea

• Topic Overview
• Biology of Neisseria gonorrhoeae
• Survival Within Host
• Screening
• Treatment
• Control/Surveillance

http//www.nature.com/genomics/images/neisseria_20
0.jpg
7
Transmission

• Does not survive in the environment, must be
  transmitted through contact
• Unprotected sex
• Contact with eyes, mouth
• Mother to child during birth

Neonatal hyperacute purulent conjunctivitis
http//www.aafp.org/afp/980215ap/morrow.html
8
Transmission

• Transmissibility dependent on
• Strain
• Male to female transmission more effective
• Higher number of organisms present in male
  urethral discharge than female vaginal secretions

http//www.biology.arizona.edu/human_bio/problem_s
ets/stds/graphics/Gonorrhea.gif
9
Structure

• Diplococcus
• Gram-negative
• Fimbriae extend several micrometers from cell
  surface

http//textbookofbacteriology.net/BSRP.html
10
http//gsbs.utmb.edu/microbook/images/fig97_2.JPG
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Systemic Infection
http//www.infocompu.com/adolfo_arthur/ingles/gono
rrea.htm
http//www.dermnet.com/thumbnailIndex.cfm?moduleID
16moduleGroupID234groupIndex0numcols0
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Infection

• N. gonorrhoeae attaches to mucosal cells via pili
  and other surface proteins
• Induces production of inflammatory cytokines by
  epithelial cells

http//www.brown.edu/Courses/Bio_160/Projects1999/
av/gonorrhea.html
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Infection
http//www.ncbi.nlm.nih.gov/books/bv.fcgi?ridmmed
.figgrp.898
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Survival Within Host

• Evades host immune system by changing surface
  proteins
• Often asymptomatic infection
• The RdgC protein is required for efficient pilin
  antigenic variation

http//www.brown.edu/Courses/Bio_160/Projects1999/
av/gonorrhea.html
15
Antigenic Variation

• Pilus promotes attachment of gonococcal cell to
  host epithelial cell
• Must retain some consistency
• Conserved N-terminal and variable C-terminal
  regions
• Constant regions
• Semi-variable regions
• Hypervariable regions
• Phase variation from piliated to non-piliated

16
Immune Memory

• Infection history did not alter antibody levels
  in patients with current infection
• Suggests immunological memory not induced by
  uncomplicated gonococcal infections
• Local and systemic immune responses to gonococci
  extremely modest
• Slight increase in serum immunoglobulin G (IgG)
  in infected males
• Slight increase in serum IgA1 antibodies in
  infected females

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Survival Within Host

• Pili, outer membrane proteins, lipopolysaccharides
  
• Binding to epithelial surfaces
• Passage through epithelium
• Interaction with phagocytes
• Variations in outer membrane protein (P1, Por)
• Requires
• Carbon dioxide
• Sulfur in form of cysteine
• Iron

http//www.med.monash.edu.au/assets/images/microbi
ology/gono.jpg
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Antimicrobial Resistance

• Gonococcal strains resistant to
• Penicillins
• Tetracyclines
• Spectinomycin
• Fluoroquinolones
• Presently, ciprofloxacin and ofloxacin
  recommended by CDC for treatment

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Biotechnology

• Oligonucleotide chips now used to screen for
  antimicrobial resistance
• Point mutations in the gyrA and parC genes
• Determine the prevalence of ciprofloxacin-resistan
  t strains
• Results identical to sequencing results
• Rapid and reliable analysis

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Gonorrhea

• Topic Overview
• Biology of Neisseria gonorrhoeae
• Survival Within Host
• Screening
• Treatment
• Control/Surveillance

http//thailabonline.com/bacteria7.htm
21
Screening

• Gold Standard
• Nucleic acid amplification assays
• Polymerase chain reaction
• Cell culture to confirm diagnosis
• Oxidase positive

http//education.med.nyu.edu/courses/microbiology/
courseware/infect-disease/Gram_Neg_Bacilli5.html
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Types of Tests

• Gram-Stained Smear
• Sensitivity reduced in asymptomatic infections
• Less that 50 sensitive as cell culture
• Not useful in rectal infections

http//www.lahey.org/Medical/InfectiousDiseases/ID
_Gonorrhea.asp
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Types of Tests

• Culture Based Systems
• High degree of specificity
• Expensive
• Trained personnel
• Media requirements
• Presumptive identification
• Growth on selective GC agar, gram stain, oxidase
  and superoxol positivity

http//www.asu.edu/it/spotlight/archive/genesis/
24
Types of Tests

• Antigen Detection and Enzyme Immunoassays
• Extensively investigated
• Low/high prevalence
• Symptomatic/asymptomatic
• Few to no situations for which this assay
  recommended
• Because of antigenic variation

http//wfrc.usgs.gov/research/fish20populations/S
TMaule5.htm
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Types of Tests

• DNA Probe Hybridization
• Specific chemiluminescent label on probe
• Available commercially
• 85 sensitivity
• 99 specificity

http//www.ebiotrade.com
26
Types of Tests

• Nucleic Acid-Based Amplification Assays (NAAT)
• 95 accurate
• False positives due to specimen
  cross-contamination, environmental contamination

http//www.biologicalprocedures.com/bpo/arts/1/6/m
6.htm
27
Current Screening

• No test for samples from all major sites of
  gonococcal infection
• Rapid
• Inexpensive
• Reliable
• Such a test would improve case-finding
• Efficient treatment
• Disease management

28
Gonorrhea

• Topic Overview
• Biology of Neisseria gonorrhoeae
• Survival Within Host
• Screening
• Treatment
• Control/Surveillance

http//neisseria.org/ng/images/
29
Treatment
http//www.cdc.gov/STD/treatment/4-2002TG.htmGono
coccal
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Treatment

• Fluoroquinolones

Levofloxacin
Ciprofloxacin
http//www.ncbi.nlm.nih.gov/books/bv.fcgi?ridmmed
.figgrp.686
http//www.alchemchina.com/products/apis_l.files/L
evofloxacin.gif
Ofloxacin
http//www.m-ww.de/pharmakologie/arzneimittel/anti
infektiva/antibiotika/ofloxacin.html
31
Treatment

• Ceftriaxone (Rocephin)
• Single dose intramuscularly
• Introduced as treatment in 1985
• Retained resistance
• Beta-lactam antibiotic
• Action against penicillinase

http//www.m-ww.de/pharmakologie/arzneimittel/anti
infektiva/antibiotika/ceftriaxon.html
32
Treatment

• Possible co-infection with Chlamydia trachomatis

Azithromycin
Doxycycline
http//www.cbwinfo.com/Pharmaceuticals/Structures/
Doxycycline.gif
http//www.bmb.leeds.ac.uk/mbiology/ug/ugteach/icu
8/images/antibiotics/azithromycin.gif
33
Vaccine

• Hard to develop
• No animal model
• No immune memory to Neisseria gonorrhoeae
• Antigenic variation strategy
• Difficulty finding target common to all strains
• Research continues to identify possible vaccine
  targets
• DNA vaccines
• Mucosal immunization

34
Gonorrhea

• Topic Overview
• Biology of Neisseria gonorrhoeae
• Survival Within Host
• Screening
• Treatment
• Control/Surveillance

http//www.mediscan.co.uk/cfm/img_coll.cfm?action
searchimageID020864collectionID21nameElectro
n20Micrographslognk
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Prevention

• Abstinence
• Safe/smart sex
• Barrier contraceptives
• Educational programs
• Reduce misuse of antimicrobials

http//www.pueblo.gsa.gov/cic_text/health/contrace
pt/condom.gif
36
Governmental Programs

• Health Canada
• Educational plans
• STD Screening
• Free STD clinics

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Governmental Programs

• CDC Gonococcal Isolate Surveillance Project
  (GISP)

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Conclusions

• More research
• Reliable, fast screening
• Preventative therapeutics
• Non-biotechnological interventions
• Prudent antimicrobial use

http//www.agma.med.uni-giessen.de/cfagma/andro/ve
rz.dbm
39
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